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EC number: 202-723-9 | CAS number: 99-04-7
Endpoint summary
Administrative data
Link to relevant study record(s)
Description of key information
m-Toluic acid is rapidly excreted in urine as methylhippuric acid via the glycine conjugate route.
Key value for chemical safety assessment
- Bioaccumulation potential:
- no bioaccumulation potential
Additional information
The toxicokinetic properties of m-toluic acid are described in the OECD SIAR 2003 for m-toluic acid (CAS 99 -04 -7) as follows:
m-Xylene is identified as a structurally related chemical of m-toluic acid because m-toluic acid is the first-step metabolite (the oxidation of one methyl side chain) of m-xylene. Six reports on the toxicokinetics and metabolism of m-toluic acid and structurally related chemicals such as xylenes, toluene and benzoic acid were reviewed. Four studies reported, in summary, that xylene and toluene were oxidized mainly to methylbenzoic acid and benzoic acid respectively, which in turn were conjugated with glycine to produce methylhippuric acid and hippuric acid, then excreted in the urine [Riihimaki V. et. al., 1979 b] [Riihimaki V. et. al., 1984] [Amsel et al., 1969] [Sedivec et al., 1976].
One study reported the metabolism of m-methyl benzoic acid (m-toluic acid), benzoic acid, m-methyl hippuric acid and hippuric acid [Riihimaki V. et. al., 1979 a]. This was identified as the key study because it was a well organized study on m-toluic acid. The study is summarized below.
Urine samples from a volunteer weighing 70 kg who was exposed to separate doses of 41 micromoles of benzoic acid, an intermediate metabolite of toluene, and 33.5 micromoles of hippuric acid, a final metabolite of toluene, m-methylbenzoic acid (m-toluic acid), an intermediate metabolite of m-xylene, and m-methyl hippuric acid, a final metabolite of m-xylene, indicated total recovery of the compound through renal excretion via the kidneys. The measured urinary elimination of ingested m-toluic acid was complete in all cases of m-methylbenzoic acid (m-toluic acid), and m-methylhippuric acid. The excretion of both the benzoic acid and methylbenzoic acid conjugates was rapid for some 4-5 hr after the ingestion of the acids, the excretion rate constants being on the order of 1.0 h-1. Only traces of free benzoic acid and methylbenzoic acid were detected in the urine after the compounds were ingested [Riihimaki V. et. al., 1979 a].
Conclusion:
m-Toluic acid is rapidly excreted in urine as methylhippuric acid via the glycine conjugate route.
References:
Amsel L. P. et al., Drug Biotransformation Interaction in Man II: A Pharmacokinetic Study of the Simultaneous Conjugation of Benzoic and Salicylic Acids with Glycine, Journal of Pharmaceutical Sciences, Vol. 58, No. 3, Page 321-326, 1969
OECD SIDS/SIAR 2003: m-toluic acid (CAS 99-04-7). SIDS initial assessment report for SIAM 16,Unep publications.
Riihimaki V. et al, Urinary Disposition of Ethylbenzene and m-xylene in man following separte and combined exposure, International archives of occupational and environmental health, Vol. 54. No.4, pages 355-363, 1984
Riihimaki V. et al., Kinetics of m-Xylene in man, Scand j. work environ. & health, 5, 217 - 231, 1979b
Riihimaki V., Conjugation and Urinary Excretion of Toluene and m-Xylene Metabolites in a Man, Scandinavian Journal of Work, Environmental and Health, Vol.5, pages 135 - 142, 1979a
Sedivic V. et al., The Absorption, Metabolism, and Excretion of Xylenes in Man, International archives of occupational and environmental health, Vol. 37, pages 205-217, 1976
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